Field of the Invention
The present invention relates generally to the fields of virology, infectious disease and medicine. More specifically, the invention relates to methods of treating a variety of Coronavirus infections in humans.
Description of the Related Art
Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus, and to date no antiviral or therapeutic has been approved for treating patients. Since September 2012, 206 cases, including 86 deaths, have been attributed to infection with MERS-CoV. Currently, supportive care remains the only available treatment option. As the number of cases continues to rise and the geographic range of the virus increases, there is a growing urgency to develop therapeutic interventions.
Prior to 2002, coronaviruses were not considered to be significant human pathogens. Other human coronaviruses such as HCoV-229E and HCoV-OC43 resulted in only mild respiratory infections in healthy adults. In 2002, however, severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in Guangdong Province, China. This virus rapidly spread to 29 different countries, resulting in 8,273 confirmed cases and 775 (9%) deaths (1). While SARS-CoV predominantly impacted Southeast Asia, with significant outbreaks throughout China, Hong Kong, Taiwan, Singapore, and Vietnam, the virus was carried outside the region. Importation of the virus into Canada resulted in 251 confirmed cases and 44 deaths (1).
In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV), was detected in a patient with severe respiratory disease in Saudi Arabia. To date, 636 laboratory-confirmed cases of MERS-CoV infection have been reported, including 193 deaths, across nine countries. The clinical features of MERS-CoV infection in humans range from asymptomatic to very severe pneumonia with the potential development of acute respiratory distress syndrome, septic shock, and multiorgan failure resulting in death. Since the first case of MERS-CoV infection was reported in September 2012 and the virus was isolated, significant progress has been made toward understanding the epidemiology, ecology, and biology of the virus (2). Several assays for the detection of acute infection with MERS-CoV by real-time reverse transcription (RT)-PCR have been developed and are in widespread use (3). Over 30 whole- or partial-genome sequences from different MERS-CoV-infected patients have been posted to GenBank, and phylogenetic trees have been published (3). Dipeptidyl peptidase 4 (also known as CD26) has been identified as the functional cellular receptor for MERS-CoV (4, 5). Ecological studies have suggested that the virus is of animal origin and is most closely related to coronaviruses found in a number of species of bats, with MERS-CoV viral sequences now found in camels in Saudi Arabia (6-9). Interestingly, a subset of MERS-CoV patients reported close contact with camels. Camels may constitute an intermediate animal host, since camel serum samples collected in 2003 and 2013 had antibodies to MERS-CoV, indicating that MERS-CoV circulates in camels (10-12). The recent development of an animal model for MERS-CoV with adenovirus vectored human DPP4 in mice will now allow for further pathogenesis studies with various MERS-CoV strains (13).
The emergences of both SARS-CoV and MERS-CoV have demonstrated the importance of coronaviruses as emerging human pathogens. In July 2013, the International Severe Acute Respiratory & Emerging Infection Consortium (ISARIC) compiled a list of drugs for treatment of MERS-CoV infection based on experience in treating SARS-CoV infection and pandemic influenza (14). The most promising and clinically available drugs were ribavirin and interferon (IFN) since they demonstrated efficacy in an in vivo model for MERS-CoV infection (15, 16). This combination has failed to demonstrate benefit in the small number of severely ill MERS-CoV patients treated (17). Outside ribavirin and IFN, the ISARIC recommendations had few alternatives for treating clinicians. Recently, mycophenolic acid (MPA) and IFN-β were shown to be highly effective against MERS-CoV infection in vitro. The activity of MPA was specific to MERS-CoV, with little activity observed against SARS-CoV infection (18, 19).
Thus, the prior art is deficient in compositions and methods to treat respiratory syndrome coronaviruses. The present invention fulfills this longstanding need and desire in the art.